Abstract Cardiovascular disease (CVD) has been the leading killer of Americans for decades. CVD is also our nation?s costliest chronic disease. In 2014, stroke and heart failure were the most expensive chronic conditions in the Medicare fee-for-service program. Based on prevalence, death rates, disability and cost, CVD will continue to be the most burdensome disease Americans will face in the next decades. It is estimated that total costs related to CVD are more than $ 500 billion [AHA]. Although there are other modalities used to diagnose heart disease, myocardial SPECT remains the best diagnostic tool for assessing myocardial ischemia, and thus the extent of CAD and its prognosis. Myocardial SPECT scans are by far the most common procedures in US nuclear medicine departments. For these reasons, we can expect that significant improvements in the efficacy of myocardial SPECT will have major impacts on patient health and medical practice. Many of the limitations of myocardial SPECT imaging originate in deficiencies of the gamma camera. Recently, a new generation of cardiac SPECT cameras have been developed that make use of pixelated CdZnTe (CZT) detectors that directly read out electrical signals from interacting gamma rays. These cameras demonstrate improved spatial resolution, detection efficiency and energy resolution over conventional gamma cameras. The initial results from this first generation of CZT cardiac SPECT cameras seem promising. However, problems with CZT may limit the possibility of another CZT camera generation with larger CZT detectors and improved performance. CZT crystals are difficult to grow; good CZT detectors are difficult to produce, the yield is low, and they are consequently very expensive. This application proposes to develop imaging detectors from thallium bromide (TlBr), a dense, high Z, wide band gap semiconductor. TlBr has several advantages over CZT including significantly lower melting point, as-grown high resistivity at room temperature, higher Z and density so less material is required to achieve a given detection efficiency and higher mobility-lifetime product of holes making efficient orthogonal strip detectors feasible. RMD proposes to demonstrate detector modules for use in cardiac SPECT imaging that can be used in existing cardiac semiconductor detector cameras, and that should improve their performance. These detector modules will use a different readout technique, orthogonal strip detection that reduces the number of electronic channels required to read out N2 ?pixels? from N2 for a conventional pixelated detector to 2N. RMD?s goal is to develop TlBr as a more efficient, less costly alternative to CZT for cardiac SPECT imaging. During Phase I TlBr orthogonal strip detectors with various areas and strip pitch were fabricated and characterized. The feasibility of utilizing TlBr orthogonal strip detectors for cardiac SPECT was demonstrated. During Phase II larger area imaging modules will be developed that can be compared with existing CZT based modules in cardiac SPECT scanners.